NOTE: The policies, guidelines, terms, and conditions
stated in this announcement may differ from those used by the NIH. Where
this Funding Opportunity Announcement (FOA) provides specific written
guidance that may differ from the general guidance provided in the grant application
form, please follow the instructions given in this FOA.

The FDA does not follow the NIH Page Limitation Guidelines
or the NIH Review Criteria. Applicants are encouraged to consult with FDA Agency Contacts for additional information
regarding page limits and the FDA Objective Review Process.

FDA is currently developing a comprehensive systems model
of the opioid's crisis. The model will serve as a tool to help FDA assess and
communicate the complex issues underlying the crisis and the potential
impacts of possible policy actions. The primary objective of this funding
opportunity is to provide supporting research that will help FDA enhance its systems
model. The results of this supporting research will help FDA improve and expand
the model and generate new insights that can better inform policy making by
FDA, and others.

Key Dates

Posted Date

May 9, 2019

Open Date (Earliest Submission Date)

May 10, 2019

Letter of Intent Due Date(s)

May 30, 2019

Application Due Date(s)

July 10, 2019, by 11:59 PM Eastern Time.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

Applicants should be aware that on-time submission means
that an application is submitted error free (of both Grants.gov and eRA
Commons errors) by 11:59 PM Eastern Time on the application due date.

Late
applications will not be accepted for this FOA.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

July 2019

Advisory Council Review

Not Applicable

Earliest Start Date

September 1, 2019

Expiration Date

July 11, 2019

Due Dates for E.O. 12372

Not Applicable

Required
Application Instructions

It is critical that applicants follow the Research (R) Instructions
in the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH
Guide for Grants and Contracts). Conformance to all requirements (both
in the Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

In 2018, FDA Center for Drug Evaluation and Research (CDER)
began an effort to develop a comprehensive systems model of the opioid crisis. The
purpose of the model is to help FDA better understand: a) the complexity of the
underlying mechanisms of the crisis, and b) potential short- and long-term
impacts of its policies — both desired outcomes and unintended consequences. FDA
intends to leverage the model as a practical tool to inform FDA
priority-setting decision-making about potential policies. Given the model’s
integrative perspective, this effort may eventually provide insights into
policy-making beyond FDA as well. FDA's opioids systems model project coincides
with complementary research and modeling efforts undertaken by both the National
Institute on Drug Abuse (NIDA) and the Centers for Disease Control and
Prevention (CDC).

FDA's current opioids systems model employs system dynamics
modeling approach, which is particularly well-suited to this problem for two
reasons. First, the opioid crisis is complex, with multiple interacting
feedbacks, time delays, and dynamics that evolve over time and lead to
unforeseen or unintended outcomes. A systems model can provide the integrative
perspective needed to guide regulatory decision-making under such
circumstances. Second, there are large gaps and uncertainties in data relevant
to the crisis. Simulation models allow rapid and extensive sensitivity analysis
to help address these uncertainties.

The formal architecture of the current model has taken shape
based on a review of the literature and numerous interviews with experts in
government, academia, and professional practice. This architecture is then
transformed into a quantitative simulation model that will be quantified,
validated, and eventually used for analysis. FDA's opioids systems model
focuses on trajectories of opioid use, including: initial exposure to prescription
opioids; opioid use, abuse, and misuse; development of opioid use disorder
(OUD); use of illicit opioids; opioid overdose, death, and harm reduction; and
OUD treatment and relapse. The model identifies the influences on these
processes, including situational, behavioral, and motivational factors. FDA's
opioids systems model will also be fully transparent and documented, as well as
publicly available, for further reproducibility and validation.

FDA's opioids systems model is being built upon academically
rigorous standards and careful assessment of the currently best available
evidence of the opioids system. At its initial stage the systems model is
considered a “baseline” dynamic model limited in current scope and
quantification. The model has been developed to enable continual improvements,
expansion, and adaptation as the complexities of the crisis change. Thus, there
is a continual need to enhance the model by refining the underlying model
structure, refining the quantification of the model parameters, expanding the
scope as appropriate, and transforming the model into a practical policy
analysis and communication tool.

Research
Objective

FDA seeks research that can supplement its opioids systems
model efforts. This may involve research into dynamic systems or complementary
modeling development, simulation and estimation techniques, data synthesis or
validation, behavioral research, or a combination of these. The research
objectives are: to identify key areas of focus and convene appropriate subject
matter experts, and to help advance regulatory science by improving the
understanding of the opioid crisis and its underlying factors and mechanisms.
This research will inform regulatory science by advancing the scientific
discussion of key policy research topics of interest to the FDA and potentially
other federal agencies, healthcare professionals, patients, and academic
researchers.

The goal of this funding opportunity is to advance research
in several key areas of interest to the FDA as it pertains to opioids and other
relevant federal agencies with diverse expertise, and to inform and support the
advancement of regulatory science priorities.

Specific objectives of this collaboration include:

a. Working collaboratively with FDA to identify and
prioritize pressing research issues related to the key areas of interest

b. Conducting research and reviews of relevant literature

c. Researching and assisting with model development

d. Convening expert stakeholders in focused, substantive
discussions of these issues, and identifying and exploring potential strategies
for resolving them

e. Developing reports that summarize the background research
and discussion at each meeting, and posting these reports for public access to
promote external interest and advance public understanding of key research
issues; and

f. Helping to make research results and reports actionable
by FDA, industry, and other stakeholders.

AREAS
OF RESEARCH

There are numerous potential opportunities to enhance FDA's
opioids systems model, which may include (but are not limited to) the areas
listed below. FDA does not necessarily expect the Awardee to be able to fully
complete all areas of research with this funding opportunity. FDA expects the
Awardee to be able to at least explore and advance research in all these areas,
and to more fully complete research in as many areas as possible.

1. Enhance modeling of utilization, effectiveness, and
outcomes of treatment for opioids use disorder (such as Medication-Assisted
Treatment (MAT) and behavioral therapy). Experts agree that the only plausible
way out of crisis for individuals is probably via treatment. However, there is
a range of treatments with varying degrees of success. In addition, there are
nuances with success rates, such as how long a patient stayed in the program
and how many times he/she relapsed. In addition, other factors such as
insurance, availability of treatment service, and accessibility of treatment
service all play significant roles in efficacy of a particular treatment
regimen. FDA's model currently only incorporates these concepts related to treatment
superficially. FDA would like to dive deeper into the treatment component and
to better understand, model, and quantify the underlying mechanisms at play in
determining the efficacy of treatments. In addition, FDA would like to explore
how these mechanisms affect policies by federal and local agencies.

3. Incorporate modeling of mental health component and other
comorbidities of opioid use disorder. It is well understood that opioid use
disorder typically goes hand in hand with mental health issues, and that the
risk of developing opioid use disorder can be greater if comorbidities are
present. This also affects the rates of intentional and unintentional overdose
deaths. FDA would like to expand research in this area and improve the current
model by incorporating this concept both qualitatively and quantitatively.

4. Research and enhance the modeling of potential
interventions of most interest to the FDA. Of particular interest are potential
interventions involving Naloxone distribution, and how those interventions can
affect overdose death. FDA would like to build and perform detailed scenario
analysis evaluating different policies regarding Naloxone availability,
prescription, and distribution.

5. Research and enhance modeling of the supply utilization
of illicit opioids such as heroin, synthetic opioids such as fentanyl, and
polysubstance use. This would include adding diverted and counterfeited Rx
opioids into the current model. Currently FDA has limited visibility into the
illicit opioid use in the existing model. The rate of transition from Rx opioid
use/misuse/abuse and use disorder to illicit opioids also depends on their
availability and prices. FDA would like to incorporate these as well as the
illicit Rx opioids market in the model both qualitatively and quantitatively.

6. Research and expand integration of social determinants
into the systems model. Social surroundings, family influences and stigma play
an important role both in developing use disorders and seeking and receiving
required treatment/therapy. The current model only briefly touches upon these concepts
and FDA would like to research how the model can be expanded to include a
meaningful modeling of their influences on the crisis as a whole, qualitatively
and quantitatively.

7. Appropriately harnessing social media data to inform
FDA's systems model. Social media has a wealth of potentially relevant and
useful information that may help us improve FDA's understanding about
underlying behavioral aspects (e.g. how people transition from Rx opioid misuse
to using heroin). FDA would like to explore this source using data mining and
machine learning approaches to improve the model.

APPROACH

Achieving these research objectives requires bringing
together input from a wide range of relevant data from public and private data
sources and subject matter experts. In addition, this input process should be
timely, well-informed, candid, thoughtful, thorough, and well-documented. FDA
is therefore seeking to establish a cooperative agreement with a qualified
awardee with experience in the conduct of the needed research, workshops and
other meetings as necessary, and related work.

The awardee will conduct research and engage in model
building and quantification activities to expand and improve the opioids systems
model, in areas important to FDA policy making. Where expert interviews are
needed, the awardee will conduct background research prior to expert
engagement, use input gathered to develop models and prepare white papers and
research reports.

FDA's current "baseline” dynamic model has been built
using system dynamics modeling formalism and has been executed in Vensim
software platform developed by Ventana Systems (vensim.com). Any sub models
produced as result of this research will have to feed in to the FDA's baseline
model and be compatible with it. These additions and improvements to FDA's
"baseline" model will take place with FDA input and discussion.

Scope:

Inherent in the cooperative agreement award is substantive
involvement by the awarding agency. Accordingly, FDA will have substantive
involvement in the programmatic activities funded by this Cooperative
Agreement. Substantive involvement includes, but is not limited, to the
following:

FDA will provide guidance and assistance and will work
closely with the research team in the identification of key research objectives
and providing subject matter expertise. In addition to the enhancements to the
development of the model in above said areas (i.e. drug utilization/
prescription and OUD treatment) FDA will work closely with the research team on
the quantification of the model and policy evaluation analysis using the model.

Cooperative Agreement: A support mechanism used when there
will be substantial Federal scientific or programmatic involvement.
Substantial involvement means that, after award, FDA scientific or program
staff will assist, guide, coordinate, or participate in project activities. See
Section VI.2 for additional information about the substantial involvement for
this FOA.

Application Types Allowed

New

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Clinical Trial?

Not Allowed: Only accepting applications that do not
propose clinical trials)

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon FDA appropriations
and the submission of a sufficient number of meritorious applications. Award(s)
will provide one (1) year of support.

FDA CDER intends to fund up to $1,000,000, for fiscal year
2019 in support of this grant program.

It is anticipated that 1 award will be made, not to exceed
$1,000,000 in total costs (direct plus indirect).

Award Budget

Application budgets need to reflect the actual needs of
the proposed project and should not exceed the following in total costs
(direct and indirect):

YR 01: $1,000,000

Award Project Period

The scope of the proposed project should determine the
project period. The maximum project period is 1 year.

HHS grants policies as
described in the HHS
Grants Policy Statement will apply
to the applications submitted and awards made from this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for FDA support as Public or Private
Institutions of Higher Education:

Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible
to apply.
Foreign components, as defined in the HHS
Grants Policy Statement, are not allowed.

Required
Registrations

Applicant
Organizations

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. Failure to complete registrations in advance of a due date is not a
valid reason for a late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM)–
Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number to register in eRA Commons. Organizations can
register with the eRA Commons as they are working through their SAM or
Grants.gov registration, but all registrations must be in place by time of
submission. eRA Commons requires organizations to identify at least one Signing
Official (SO) and at least one Program Director/Principal Investigator (PD/PI)
account in order to submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.
PD(s)/PI(s) should work with their organizational officials to either
create a new account or to affiliate their existing account with the applicant
organization in eRA Commons. If the PD/PI is also the organizational Signing Official,
they must have two distinct eRA Commons accounts, one for each role. Obtaining
an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for FDA support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

The FDA will not accept duplicate or highly overlapping
applications under review at the same time. This means that the FDA will
not accept:

A new (A0) application that is submitted before issuance of the
summary statement from the review of an overlapping new (A0) or resubmission
(A1) application.

A resubmission (A1) application that is submitted before issuance
of the summary statement from the review of the previous new (A0) application.

Section IV. Application and Submission Information

1. Requesting an
Application Package

The application forms package specific to this opportunity
must be accessed through ASSIST, Grants.gov Workspace or an institutional
system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are
available in Part 1 of this
FOA. See your administrative office for instructions if you plan to use an
institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Research (R) Instructions
in the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Letter of Intent

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows FDA staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1.
Overview Information, prospective applicants are asked to submit a letter
of intent that includes the following information:

Descriptive title of proposed activity

Name(s), email address(es), and telephone number(s) of the
PD(s)/PI(s)

A technical session will be held for prospective applicants
in JUNE 2019. The conference call information will be provided to prospective
applicants that submit a letter of intent. The technical session will provide
an overview of the submission requirements and allow prospective applicants an
opportunity to ask questions regarding the application process. Participation
in the technical session is optional, but strongly encouraged.

Page Limitations

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed, with the following exceptions or additional
requirements:

For this specific FOA, the Research Strategy section is
limited to 30 pages.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed.

R&R Budget

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Applications requesting multiple years of support must complete
and submit a separate detailed budget breakdown and narrative justification for
each year of financial support requested.

If an applicant is requesting indirect costs as part of their
budget, a copy of the most recent Federal indirect cost rate or F&A
agreement must be provided as part of the application submission. This
agreement should be attached to the RESEARCH & RELATED Other Project
Information Component as line #12 'Other Attachments'.

If the applicant organization has never established an indirect
cost rate and/or does not have a negotiated Federal indirect cost rate
agreement, a de minimis indirect cost rate of 10 percent (10%) of modified
total direct costs (MTDC) will be allowed. MTDC means all direct salaries and
wages, applicable fringe benefits, materials and supplies, services, travel,
and subaward and subcontracts up to the first $25,000 of each subaward or
subcontract. MTDC excludes equipment, capital expenditures, charges for
patient care, rental costs, tuition remission, scholarships and fellowships,
participant support costs and the portion of each subaward and subcontract in
excess of $25,000.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans as provided in the SF424 (R&R)
Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

Appendix:

Only limited Appendix materials are allowed. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

PHS Human Subjects and Clinical Trials Information

When involving FDA-defined human subjects research, clinical
research, and/or clinical trials (and when applicable, clinical trials research
experience) follow all instructions for the PHS Human Subjects and Clinical
Trials Information form in the SF424 (R&R) Application Guide, with the
following additional instructions:

If you answered “Yes” to the question “Are Human Subjects
Involved?” on the R&R Other Project Information form, you must include at
least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials
Information form or Delayed
Onset Study record.

Study
Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide
must be followed with the following additional instructions:

Delayed
Onset Study

Note: Delayed
onset does NOT apply to a study that can be described but will not start
immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide
must be followed.

3. Unique Entity Identifier
and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the
requirement for obtaining a unique entity identifier and for completing and
maintaining active registrations in System for Award Management (SAM), NATO
Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and
Grants.gov

4. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to
submit applications before the due date to ensure they have time to make any
application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, FDA’s electronic system for grants
administration. eRA Commons and Grants.gov systems check the application
against many of the application instructions upon submission. Errors must be
corrected and a changed/corrected application must be submitted to Grants.gov
on or before the application due date and time. If a Changed/Corrected
application is submitted after the deadline, the application will be considered
late. Late applications
will not be accepted for this FOA.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit How to
Apply – Application Guide. For assistance with application submission,
contact the Application Submission Contacts in Section
VII.

Important
reminders:

All PD(s)/PI(s) must include their eRA Commons ID in
the Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to FDA. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS
number it provides on the application is the same number used in the
organization’s profile in the eRA Commons and for the System for Award Management.
Additional information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness and compliance with application instructions by the assigned
Grants Management Specialist and responsiveness by components of participating organizations,
FDA. Applications that are incomplete, non-compliant and/or nonresponsive will
not be reviewed.

Post Submission Materials

Post-submission materials are those submitted after
submission of the grant application but prior to objective review. They are not
intended to correct oversights or errors discovered after submission of the
application. FDA accepts limited information between the time of initial
submission of the application and the time of objective review. Applicants
must contact the assigned Grants Management Specialist to receive approval, prior
to submitting any post submission materials. Acceptance and/or rejection of any
post submission materials is at the sole discretion of the FDA. Any inquiries
regarding post submission materials should be directed to the assigned Grants
Management Specialist.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process.

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit.

Significance (20 Points)

Does the project address an important problem or a
critical barrier to progress in the field? Is the prior research that serves as
the key support for the proposed project rigorous? If the aims of the project
are achieved, how will scientific knowledge, technical capability, and/or
clinical practice be improved? How will successful completion of the aims
change the concepts, methods, technologies, treatments, services, or
preventative interventions that drive this field?

Investigator(s) (20 Points)

Are the PD(s)/PI(s), collaborators,
and other researchers well suited to the project? If Early Stage Investigators
or those in the early stages of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? If the project is
collaborative or multi-PD/PI, do the investigators have complementary and
integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project?

Innovation (10 Points)

Does the application challenge and
seek to shift current research or clinical practice paradigms by utilizing
novel theoretical concepts, approaches or methodologies, instrumentation, or
interventions? Are the concepts, approaches or methodologies, instrumentation,
or interventions novel to one field of research or novel in a broad sense? Is a
refinement, improvement, or new application of theoretical concepts, approaches
or methodologies, instrumentation, or interventions proposed?

Approach (30 Points)

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project? Have
the investigators included plans to address weaknesses in the rigor of prior
research that serves as the key support for the proposed project? Have the
investigators presented strategies to ensure a robust and unbiased approach, as
appropriate for the work proposed? Are potential problems, alternative
strategies, and benchmarks for success presented? If the project is in the early
stages of development, will the strategy establish feasibility and will
particularly risky aspects be managed? Have the investigators presented
adequate plans to address relevant biological variables, such as sex, for
studies in vertebrate animals or human subjects?

If the project involves human subjects and/or FDA-defined
clinical research, are the plans to address

1) the protection of human subjects from research
risks, and

2) inclusion (or exclusion) of individuals on the
basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion
of individuals of all ages (including children and older adults), justified in
terms of the scientific goals and research strategy proposed?

Past Performance (20 Points)

Does the application highlight how previous work done
and knowledge gained is relevant to the

project being proposed? Have the
collaborators demonstrated ability in modeling complex systems to support policy
analysis?

Additional Review Considerations

As applicable for the project proposed, reviewers will
evaluate the following additional items but will not give separate scores for
these items, and should not consider them in providing an overall score.

Protections for Human Subjects

For research that involves human
subjects but does not involve one of the categories of research that are
exempt under 45 CFR Part 46, the committee will evaluate the justification for
involvement of human subjects and the proposed protections from research risk
relating to their participation according to the following five review
criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3)
potential benefits to the subjects and others, 4) importance of the knowledge
to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human
subjects and meets the criteria for one or more of the categories of research
that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the
justification for the exemption, 2) human subjects involvement and
characteristics, and 3) sources of materials. For additional information on
review of the Human Subjects section, please refer to the Guidelines for the Review of Human
Subjects.

Inclusion of Women, Minorities, and Individuals
Across the Lifespan

When the proposed project involves
human subjects and/or FDA-defined clinical research, the committee will
evaluate the proposed plans for the inclusion (or exclusion) of individuals on
the basis of sex/gender, race, and ethnicity, as well as the inclusion (or
exclusion) of individuals of all ages (including children and older adults) to
determine if it is justified in terms of the scientific goals and research
strategy proposed. For additional information on review of the Inclusion
section, please refer to the Guidelines for the Review of Inclusion
in Clinical Research.

Vertebrate Animals

The committee will evaluate the
involvement of live vertebrate animals as part of the scientific assessment
according to the following criteria: (1) description of proposed procedures
involving animals, including species, strains, ages, sex, and total number to
be used; (2) justifications for the use of animals versus alternative models
and for the appropriateness of the species proposed; (3) interventions to
minimize discomfort, distress, pain and injury; and (4) justification for
euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia
of Animals. Reviewers will assess the use of chimpanzees as they would any
other application proposing the use of vertebrate animals. For additional
information on review of the Vertebrate Animals section, please refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether
materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Select Agent Research

Reviewers will assess the information
provided in this section of the application, including 1) the Select Agent(s)
to be used in the proposed research, 2) the registration status of all entities
where Select Agent(s) will be used, 3) the procedures that will be used to
monitor possession use and transfer of Select Agent(s), and 4) plans for
appropriate biosafety, biocontainment, and security of the Select Agent(s).

For projects involving key biological and/or chemical resources,
reviewers will comment on the brief plans proposed for identifying and ensuring
the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the
budget and the requested period of support are fully justified and reasonable
in relation to the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Objective Review Committee, using the stated review criteria.

As part of the objective review, all applications:

Will receive a written critique.

Appeals of objective review will not be accepted for
applications submitted in response to this FOA.

Applications will compete for available funds with all other
recommended applications submitted in response to this FOA. The following will
be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by objective review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

Successful applicants will be notified of additional
information that may be required or other actions leading to an award. The
decision not to award a grant, or to award a grant at a particular funding
level, is discretionary and is not subject to appeal to any FDA or HHS official
or board.

Section VI. Award
Administration Information

1. Award Notices

A formal notification in the form of a Notice of Award (NoA)
will be provided to the applicant organization for successful applications. The
NoA signed by the grants management officer is the authorizing document and
will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described
in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

Recipients of federal financial
assistance (FFA) from HHS must administer their programs in compliance with
federal civil rights law. This means that recipients of HHS funds must ensure
equal access to their programs without regard to a person’s race, color,
national origin, disability, age and, in some circumstances, sex and religion.
This includes ensuring your programs are accessible to persons with limited
English proficiency. HHS recognizes that research projects are often limited
in scope for many reasons that are nondiscriminatory, such as the principal
investigator’s scientific interest, funding limitations, recruitment
requirements, and other considerations. Thus, criteria in research protocols
that target or exclude certain populations are warranted where
nondiscriminatory justifications establish that such criteria are appropriate
with respect to the health or safety of the subjects, the scientific study
design, or the purpose of the research.

In accordance with the statutory provisions contained in
Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal
Year 2009 (Public Law 110-417), FDA awards will be subject to the Federal
Awardee Performance and Integrity Information System (FAPIIS) requirements.
FAPIIS requires Federal award making officials to review and consider
information about an applicant in the designated integrity and performance
system (currently FAPIIS) prior to making an award. An applicant, at its
option, may review information in the designated integrity and performance
systems accessible through FAPIIS and comment on any information about itself
that a Federal agency previously entered and is currently in FAPIIS. The
Federal awarding agency will consider any comments by the applicant, in
addition to other information in FAPIIS, in making a judgement about the
applicant’s integrity, business ethics, and record of performance under Federal
awards when completing the review of risk posed by applicants as described in
45 CFR Part 75.205 “Federal awarding agency review of risk posed by
applicants.” This provision will apply to all FDA grants and cooperative
agreements.

FDA considers the sharing of research resources developed
through FDA-sponsored research an important means to enhance the value and
further the advancement of research. When research resources have been
developed with FDA funds and the associated research findings published, those
findings must be made readily available to the scientific community.

Upon acceptance for publication, scientific researchers must
submit the author’s final manuscript of the peer-reviewed scientific
publication resulting from research supported in whole or in part with FDA
funds to the NIH National Library of Medicine's (NLM) PubMed Central (PMC). FDA
defines the author's final manuscript as the final version accepted for journal
publication, which includes all modifications from the publishing peer review
process. The PMC archive is the designated repository for these manuscripts for
use by the public, health care providers, educators, scientists, and FDA.
Please see the FDA Public Access Policy.

Certificates of Confidentiality – 42 U.S.C. 241(d)

Awardees are responsible for complying with all requirements
to protect the confidentiality of identifiable, sensitive information that is
collected or used in biomedical, behavioral, clinical, or other research
(including research on mental health and research on the use and effect of
alcohol and other psychoactive drugs) funded wholly or in part by the Federal
Government. See 42 U.S.C. 241(d). All research funded by FDA, in
whole or in part, that is within the scope of these requirements is deemed to
be issued a “Certificate of Confidentiality” through these Terms and
Conditions. Certificates issued in this manner will not be issued
as a separate document.

Awardees are expected to ensure that any investigator or
institution not funded by FDA who receives a copy of identifiable, sensitive
information protected by these requirements, understand they are also subject
to the requirements of 42 U.S.C. 241(d). Awardees are also responsible
for ensuring that any subrecipient that receives funds to carry out part of the
FDA award involving a copy of identifiable, sensitive information protected by
these requirements understand they are also subject to subsection 42 U.S.C.
241(d).

Additional terms and conditions regarding FDA regulatory and
Center for Drug Evaluation programmatic requirements may be part of the Notice
of Award.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (HHS)
grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and FDA
grant administration policies.

The administrative and funding instrument used for this
program will be the cooperative agreement, an “assistance” mechanism (rather
than an “acquisition” mechanism), in which substantial FDA programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, FDA's
purpose is to support and stimulate the recipients’ activities by involvement
in and otherwise working jointly with the award recipients in a partnership
role; it is not to assume direction, prime responsibility, or a dominant role
in the activities. Consistent with this concept, the dominant role and
prime responsibility resides with the awardees for the project as a whole,
although specific tasks and activities may be shared among the awardees and FDA
as defined below.

2.A.1. Principal Investigator Rights and Responsibilities

The PD(s)/PI(s) will have the primary responsibility for the
scientific, technical, or programmatic aspects of the cooperative agreement and
for day-to-day management of the project or program. The PD(s)/PI(s) will
maintain general oversight for ensuring compliance with the financial and
administrative aspects of the award, as well as ensuring that all staff have
sufficient clearance and/or background checks to work on this project or
program. This individual will work closely with designated officials within
the recipient organization to create and maintain necessary documentation,
including both technical and administrative reports; prepare justifications;
appropriately acknowledge Federal support in publications, announcements, news
programs, and other media; and ensure compliance with other Federal and
organizational requirements.

Awardees will retain custody of and have primary rights to
the data and software developed under these awards, subject to Government
rights of access consistent with current HHS, PHS, and FDA policies.

Additionally, PD/PIs will:

1. Participate in site visits or attend meetings as
requested by the FDA. A portion of the budget should be reserved for such
travel.

2. FDA may also request data be made available through
speaking engagements and publications, presentations at scientific symposia and
seminars, while making sure that confidentiality and privacy of the data is
protected.

3. The awardees will provide FDA any data obtained from
investigations if requested by FDA.

4. Any publication or oral presentation of regarding
outcomes of this grant must undergo FDA/CDER review and approval process. This
process can take 30-90 days.

2. A.2. FDA Responsibilities

An FDA Project Officer (PO) will have substantial
programmatic involvement as described below. The PO is the official responsible
for the programmatic, scientific, and/or technical aspects of assigned
applications and grants. The PO’s responsibilities include, but are not limited
to, post-award monitoring of project/program performance, including review of
progress reports and making site visits; and other activities complementary to
those of the Grants Management Officer (GMO). The PO and the GMO work as a team
in many of these activities.

Additionally, an agency program official will be responsible
for the scientific and programmatic stewardship of the award and will be named
in the award notice.

FDA will provide technical monitoring and/or guidance of the
work, including monitoring of data analysis, interpretation of analytical
findings and their significance.

FDA will assist and approve (as deemed appropriate) the
substance of publications, co-authorship of publications and data release.

Financial Reporting:

A. Cash Transaction Reports

The Federal Financial Report (FFR) has a dedicated section
to report Federal cash receipts and disbursements. For recipients, this
information must be submitted quarterly directly to the Payment Management
System (PMS) using the web-based tool. Quarterly reports are due 30 days
following the end of each calendar quarter. The reporting period for this
report continues to be based on the calendar quarter. Questions concerning the
requirements for this quarterly financial report should be directed to the PMS.

B. Financial Expenditure Reports

A required Federal Financial Report (FFR) must be submitted
annually. FDA now requires all annual financial expenditure reports to be
submitted electronically using the Federal Financial Report (FFR) system
located in the eRA Commons. This includes all initial FFRs being prepared for
submission and any revised FSR/FFRs being submitted or re-submitted to FDA.
Paper expenditure/FFR reports will not accepted.

Annual FFRs must be submitted for each budget period no
later than 90 days after the end of the calendar quarter in which the budget
period ended. The reporting period for an annual FFR will be that of the budget
period for the particular grant; however, the actual submission date is based
on the calendar quarter. Failure to submit timely reports may affect future
funding.

Performance Progress Reporting:

1. Annual progress reports are required. The Annual
Progress Report will be due as part of the Research Performance Progress Report
(RPPR).

2. Grants with Multiple Years: When multiple years are
involved, awardees will be required to submit the Research Performance Progress
Report (RPPR) annually (?).

Information regarding submitting the RPPR is available at
https://era.nih.gov/erahelp/commons/default.htm#cshid=1020

PROGRAM INCOME:

1. The grantee is required to report any Program Income
generated during the Project Period of this grant. Except for royalty income
generated from patents and inventions, the amount and disposition of Program
Income must be identified on lines 10 (l), (m), (n), and (o) of the grantee’s
Federal Financial Report (FFR) SF-425.

2. Examples of Program Income include (but are not limited
to): fees for services performed during the grant or sub-grant period, proceeds
from sale of tangible personal or real property, usage or rental fees, patent
or copyright royalties, and proceeds from the sale of products and technology
developed under the grant.

3. Any Program Income generated during the Project Period of
this grant by the grantee or sub-grantee is subject to the Addition Alternative
for Program Income and, therefore, must only be used to further the goals of
the project for which this grant was awarded.

PRIOR APPROVAL:

All requests that require prior approval must include the
award number and bear the signature of an authorized official of the grantee
business office as well as that of the PI/PD. Any requests involving funding
issues must include a new proposed budget and a narrative justification of the
requested changes. If a grantee questions whether prior approval is required
for an activity or cost, they should contact the assigned Grants Management
Specialist prior to expenditure of funds for clarification.

A final RPPR, invention statement,
and the expenditure data portion of the Federal Financial Report are required for
closeout of an award, as described in the terms and conditions of award and the HHS
Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable FDA grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.

In accordance with the regulatory requirements provided at
45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have
currently active Federal grants, cooperative agreements, and procurement
contracts from all Federal awarding agencies with a cumulative total value
greater than $10,000,000 for any period of time during the period of
performance of a Federal award, must report and maintain the currency of
information reported in the System for Award Management (SAM) about civil,
criminal, and administrative proceedings in connection with the award or
performance of a Federal award that reached final disposition within the most
recent five-year period. The recipient must also make semiannual
disclosures regarding such proceedings. Proceedings information will be
made publicly available in the designated integrity and performance system
(currently FAPIIS). This is a statutory requirement under section 872 of
Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010
of Public Law 111-212, all information posted in the designated integrity and
performance system on or after April 15, 2011, except past performance reviews
required for Federal procurement contracts, will be publicly available. Full
reporting requirements and procedures are found in Appendix XII to 45 CFR Part
75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions
regarding ASSIST, eRA Commons, application errors and warnings, documenting
system problems that threaten submission by the due date, and post-submission
issues)